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Chemical restriction of PU.1 genomic binding sites activates alternate gene networks

Blockade of primary genomic binding sites with small molecules causes redistribution of the transcription factor PU.1 to alternative binding sites; its transcriptional activity at these sites activates secondary gene networks that drive myeloid cell differentiation.

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Fig. 1: Molecular and cellular consequences of pharmacological PU.1 redistribution.

References

  1. Scott, E. W. et al. Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages. Science 265, 1573–1577 (1994). A paper reporting the essential role of PU.1 in controlling hematopoietic lineage fate.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  2. Will, B. et al. Minimal PU.1 reduction induces a preleukemic state and promotes development of acute myeloid leukemia. Nat. Med. 21, 1172–1181 (2015). A paper describing the role of PU.1 in driving the development of myeloid leukemia.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  3. Munde, M. et al. Structure-dependent inhibition of the ETS-family transcription factor PU.1 by novel heterocyclic diamidines. Nucleic Acids Res. 42, 1379 (2014). A paper describing how heterocyclic diamidines block PU.1–DNA interactions through minor groove interference.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  4. Antony-Debré, I. et al. Pharmacological inhibition of the transcription factor PU.1 in leukemia. J. Clin. Invest. 127, 4297–4313 (2017). A paper describing the proof-of-concept use of heterocyclic diamidines to target PU.1 networks in AML.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  5. Pham, T. H. et al. Mechanisms of in vivo binding site selection of the hematopoietic master transcription factor PU.1. Nucleic Acids Res. 41, 6391–6402 (2013). A paper highlighting the affinity of PU.1 for its genomic binding sites.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  6. Minderjahn, J. et al. Mechanisms governing the pioneering and redistribution capabilities of the non-classical pioneer PU.1. Nat. Commun. 11, 402 (2020). A paper highlighting the non-classical pioneer transcription factor ability of PU.1.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

Download references

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This is a summary of: Taylor, S. J. et al. Pharmacological restriction of genomic binding sites redirects PU.1 pioneer transcription factor activity. Nat. Genet. https://doi.org/10.1038/s41588-024-01911-7 (2024).

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Chemical restriction of PU.1 genomic binding sites activates alternate gene networks.
Nat Genet (2024). https://doi.org/10.1038/s41588-024-01912-6

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  • Published: 18 September 2024

  • DOI: https://doi.org/10.1038/s41588-024-01912-6

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